Illig, C., et al., in US Patent Publication US2009 0105296 A1, published Apr. 23, 2009 disclose c-FMS kinase inhibitors, derivatives of the following structural formula

pharmaceutically acceptable salts thereof; and a process for their preparation. Illig, C., et al., in Scheme 1 teach preparation of the derivatives of the above structural formula comprising reacting a compound of formula 1-5

with “a heterocyclic acid P1-WCOOH (or a corresponding salt thereof P1-WCOOM2, where M2 is Li, Na or K) where P1 is an optional protecting group (for example 2-(trimethylsilyl)ethoxymethyl (SEM) such as when W is imidazole, triazole, pyrrole, or benzimidazole) or where P1 is not present such as when W is furan . . . . The coupling can be carried out according to standard procedures for amide bond formation (see for example, M. Bodansky and A. Bodansky, The Practice of Peptide Synthesis, Springer-Verlag, NY (1984)) or by reaction with acid chlorides P1-WCOCl or activated esters P′-WCO2Rq (where Rq is a leaving group such as pentafluorophenyl or N-succinimide)”.
Illig, C., et al., in Scheme 9, further teach a process for the preparation of protected carboxylic acids of the formula P1-WCOOH or the corresponding salts of the formula P1-WCOOM2, more particularly for compounds wherein W is imidazolyl. In the process taught by Illig, C., et al., an optionally substituted imidazolyl is protected at the 1-position nitrogen, with a suitably selected protecting group such as MOM or SEM, according to known methods.
The protected imidazole is then “halogenated with a suitable reagent such as N-bromosuccinimide or N-iodosuccinimide under either electrophilic conditions in a solvent such as DCM or CH3CN or under radical conditions in the presence of an initiator such as azobis(isobutyronitrile) (AIBN) in a solvent such as CCl4” to yield the corresponding compound, wherein the 2-position on the imidazole is substituted with the corresponding halogen atom. “Halogen-magnesium exchange on” said compounds yields “the corresponding organomagnesium species, which is then reacted with a suitable electrophile”, to yield the corresponding protected ester. Alternatively, the protected imidazole is “deprotonated with a suitable base such as an alkyllithium followed by reaction with an electrophile”, to similarly yield the corresponding protected carboxylic acid of formula ester.
The protected ester can then be “hydrolyzed to” the corresponding “carboxylic acids” of formula P1-WCOOH “or carboxylate salts” of formula P1-WCOOM2 (wherein “M2 is Li, Na, or K,) using an aqueous metal hydroxide (MOH) solution, in a suitable solvent.”
WALL., M. J., et al., “Cyano-Substituted 2-Carboxylmidazoles: Synthesis of 4-Cyano-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazole-2-carboxylate Potassium Salt”, Synthesis, 2008, pp 3377-3379, No. 21 describe the synthesis of 4-cyano-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazole-2-carboxylate potassium salt where the carboxylate group is introduced via bromine-magnesium exchange on a SEM-protected cyanoimidazole followed by reaction with ethyl cyanoformate. The synthesis includes the equilibration of a regioisomeric mixture of SEM-protected imidazoles to give a single product. The process described by Wall et al. utilizes low temperatures and expensive reagents, which are not preferred for large scale process manufacture.
BARNARD, C. F. J., “Carbonylation of Aryl Halides: Extending the Scope of the Reaction”, Org. Proc. Res. Dev., 2008, pp. 566-574, Vol. 12, describes the carbonylation of aryl halides. Barnard et al., describes conditions of carbonylation which use of an inorganic base and temperature greater than 100° C., which are not preferred for large scale manufacture.
ALBANEZE-WALKER, J., et al., “Improved Carbonylation of Heterocyclic Chlorides and Electronically Challenging Aryl Bromides”, Org. Lett. 2004, pp 2097-2100, Vol. 6, No. 13, describe carbonylation of heterocyclic halides. The process described by Albenese-Walker et al. also use a reaction temperature of 100° C., which is not preferred for large scale manufacture.
There remains however, a need for a process for the preparation of compounds of formula (I), as herein described; wherein the process is suitable for large scale manufacture.